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Southern corn rust (SCR), caused by Puccinia polysora Underw (P. polysora), is a catastrophic disease affecting maize, leading to significant global yield losses. The disease manifests primarily as pustules on the upper surface of corn leaves, obscuring our understanding of its cellular heterogeneity, the maize's response to its infection and the underlying gene expression regulatory mechanisms. In this study, we dissected the heterogeneity of maize's response to P. polysora infection using single-cell RNA sequencing. We delineated cell-type-specific gene expression alterations in six leaf cell types, creating the inaugural single-cell atlas of a maize leaf under fungal assault. Crucially, by reconstructing cellular trajectories in susceptible line N110 and resistant line R99 during infection, we identified diverse regulatory programs that fortify R99's resistance across different leaf cell types. This research uncovers an immune-like state in R99 leaves, characterized by the expression of various fungi-induced genes in the absence of fungal infection, particularly in guard and epidermal cells. Our findings also highlight the role of the fungi-induced glycoside hydrolase family 18 chitinase 7 protein (ZmChit7) in conferring resistance to P. polysora. Collectively, our results shed light on the mechanisms of maize resistance to fungal pathogens through comparative single-cell transcriptomics, offering a valuable resource for pinpointing novel genes that bolster resistance to P. polysora., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated HSC-specific adiponectin overexpression and null models that demonstrate that HSC-specific adiponectin overexpression dramatically reduces liver fibrosis, whereas HSC-specific adiponectin elimination accelerates fibrosis progression. We identify a local adiponectin-peroxisome proliferator-activated receptor gamma (PPARγ) axis in HSCs that exerts a marked influence on the progression of local fibrosis, independent of circulating adiponectin derived from adipocytes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Jejunal diverticula (JD) are rare clinical conditions that are typically incidentally detected and asymptomatic. When acute complications arise, surgical exploration may be necessary for accurate diagnosis and appropriate treatment. In this report, we present a case of multiple JD complicated by gastrointestinal bleeding and review the pathogenesis, diagnosis, and treatment of JD to increase clinician awareness of this condition., Case Summary: A 70-year-old male patient with multiple JD presented with repeated massive gastrointestinal bleeding. The patient did not respond to symptomatic conservative treatment. Additional diagnostic investigations, including digestive endoscopy and abdominal angiography, did not reveal any relevant abnormalities. An exploratory laparotomy was subsequently performed, during which a segment of the bowel containing numerous diverticulum-like structures was surgically removed. Following successful discharge from the hospital, the patient did not experience any further episodes of gastrointestinal bleeding during subsequent follow-up., Conclusion: Complications caused by JD are often difficult to diagnose, and surgical exploration is sometimes the most appropriate method., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The global prevalence of people living with overweight has tripled since 1975 and more than 40% of Danish women enter pregnancy being overweight. With the increasing rates of obesity observed in children, adolescents and adults, there is an urgent need for preventive measures. Risk factors for childhood obesity include maternal overweight or obesity before conception and excessive weight gain during pregnancy. Interventions aimed at modifying maternal lifestyle during pregnancy have demonstrated minimal positive or no impact on the health of the children. The 'healthy lifestyle before and during pregnancy to prevent childhood obesity - the PRE-STORK trial' aims to provide insights into the effect of a lifestyle intervention initiated before conception and continued during pregnancy in women with overweight or obesity, on neonatal adiposity in their children., Methods and Analysis: In this randomised, two-arm, parallel-group, controlled trial, we will include 360 women with overweight or obesity (aged 18-40; body mass index 25-44 kg/m 2 ) and their partners. The women will be randomised to receive either standard of care or a lifestyle intervention focused on preconception body weight reduction, regular physical exercise, healthy diet and support from a mentor before and during pregnancy. The primary outcome is the difference in neonatal adiposity measured in their children at birth. Children conceived during the trial will constitute a birth cohort, monitoring the effects on their health until the age of 18 years., Ethics and Dissemination: The trial has been approved by the Regional Committee on Health Research Ethics in the Capital Region of Denmark (identification number H-22011403) and will be conducted in agreement with the Declaration of Helsinki. All results, whether positive, negative and inconclusive, will be disseminated at national or international scientific meetings and in peer-reviewed scientific journals., Trial Registration Number: ClinicalTrials.gov: NCT05578690 (October 2022)., Competing Interests: Competing interests: NK, JHD, RES, MLP, SF, NG, EG, LL, KKN, AA, LGG and TV are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, which is partly funded by a grant from Novo Nordisk Foundation. RES owns shares in Novo Nordisk A/S. MYJ is currently employed in Novo Nordisk A/S. FKK has served on scientific advisory panels, been part of speaker's bureaus for, served as a consultant to and/or received research support from 89bio, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gubra, Novo Nordisk, Sanofi, Structure Therapeutics, Zealand Pharma, Zucara; is a co-founder and minority shareholder in Antag Therapeutics and owns shares in Eli Lilly, Novo Nordisk and Zealand Pharma; is currently employed by Novo Nordisk. TB has received lecture fees from Novo Nordisk. LK owns shares in Novo Nordisk A/S. SF has been part of speaker's bureaus for Novo Nordisk. RB has received research grants from the Novo Nordisk Foundation. AA has received lecture fees from Eli Lilly. SST has received grants, honoraria for lectures and membership on an advisory panel for Novo Nordisk, Research grant from Embla, Horaria for lectures from Merck and Ferring. LGG owns shares in Novo Nordisk A/S. TV has served on scientific advisory panels, been part of speaker's bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GSK, Novo Nordisk, Sanofi and Sun Pharmaceuticals., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Diabetic cardiomyopathy causes end-stage heart failure, resulting in high morbidity and mortality in type 2 diabetes mellitus (T2DM) patients. Long-term treatment targeting metabolism is an emerging field in the treatment of diabetic cardiomyopathy. Semaglutide, an agonist of the glucagon-like peptide 1 receptor, is clinically approved for the treatment of T2DM and provides cardiac benefits in patients. However, the cardioprotective mechanism of semaglutide, especially its direct effects on cardiomyocytes (CMs), is not fully understood. Here, we used 8-week diabetic and obese db/db mice treated with semaglutide (200 μg·kg·d -1 , i.p.) to study its direct effect on CMs and the underlying mechanisms. Our results revealed that the consecutive application of semaglutide improved cardiac function. Increased AMPK and ULK1 phosphorylation levels were detected, accompanied by elevated [Ca 2+ ] mito . Seahorse analysis revealed that semaglutide increases ATP production via elevated basal and maximum respiration rates as well as spare respiration capacity in CMs. Transmission electron microscopy revealed improved mitochondrial morphology in the cardiomyocytes of db/db mice. On the other hand, Western blot analysis revealed increased Parkin and LC3 protein expression, indicating mitophagy in CMs. Collectively, our findings demonstrate that semaglutide directly protects CMs from high-glucose damage by promoting AMPK-dependent ATP production as well as ULK1-mediated mitophagy in db/db mice., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies. To investigate the genetic predisposition of Chinese patients to anticitrullinated protein antibody (ACPA)-positive RA, we carried out an exome sequencing study., Methods: Patients were recruited from 3 major public hospitals in Singapore: Tan Tock Seng Hospital (TTSH), Singapore General Hospital, and the National University Hospital. Controls came from an established exome collection and from the TTSH Health Control Biobank. All the participants were of Chinese descent. We performed whole-exome sequencing (WES) in 595 ACPA-positive patients with RA and 1281 controls and validated the candidate variants by genotyping 795 RA cases and 600 controls., Results: The discovery cohort yielded 73 susceptibility single-nucleotide variants (SNVs) that reached statistical significance. In the validation study with an independent cohort, 2 SNVs remained significant: PCNXL4 ( P = 1.50 × 10 -5 ) and DHRS7 ( P = 6.02 × 10 -5 ). The majority of known susceptibility foci were not captured by exome sequencing., Conclusion: In this WES study of ACPA-positive RA in Chinese patients, we discovered 2 new variants in PCNXL4 and DHRS7 associated with risk for RA.

Tauopathies cover a range of neurodegenerative diseases in which natively unfolded tau protein aggregates and spreads in the brain during disease progression. To gain insights into the mechanism of tau structure and spreading, here, we examined the biochemical and cellular properties of human full-length wild-type and familial mutant tau, ΔK280, with a deletion at lysine 280. Our results showed that both wild-type and mutant tau are predominantly monomeric by analytical ultracentrifugation. The mutant tau may lose intramolecular contacts and is significantly destabilized assessed by cross-linking mass spectrometry and urea denaturation. Moreover, the mutant tau displayed accelerated fibril formation compared to the wild-type tau. Upon cross-seeding, the wild-type tau was seeded more easily by wild-type seeds than mutant seeds showing that homotypic seeding is more efficient. The wild-type tau was successfully converted to fibrils with mutant signatures by mutant seeds. Live cell cross-correlation fluorescence spectroscopy studies indicated that wild-type tau forms trimeric species and the mutant tau forms a larger assembly and processes higher cell-to-cell transmission. Overall, these findings shed light on the fundamental mechanisms of tau structure/stability, aggregation, and seeding to facilitate future therapeutic development for tauopathies., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to assess whether dual anti-HER2 therapy with trastuzumab and pertuzumab increases early cardiac toxicity compared to trastuzumab alone in breast cancer (BC) patients receiving postoperative radiation therapy (RT)., Methods: Consecutive operable BC patients receiving postoperative RT and trastuzumab with or without pertuzumab between January 2017 and September 2020 at seven tertiary hospitals in China were retrospectively reviewed. Cardiac examinations included echocardiography, electrocardiogram (ECG), NT-proBNP, and cTnI at baseline before RT and during the follow-up. The cardiac event is any new-onset symptomatic heart disease or abnormality in the cardiac examination after RT., Results: In total, 681 patients were enrolled in the analysis, of whom 567 were treated with trastuzumab-alone and 124 patients received dual anti-HER2 therapy. The median follow-up was 11 months. Multivariate analysis showed that left-sided breast cancer (HR 2.38; 95%CI 1.65-3.44, p < 0.001) and IMN RT (HR 1.47; 95 % CI 1.01-2.15, P-value = 0.047) are independent risk factors for ECG abnormalities. Age >50 years is an independent risk factor for developing LVDD (HR 5.16; 95%CI 1.17-22.73, P-value = 0.030). Dosimetric analysis showed that patients who developed subclinical cardiac events had increased mean heart dose (412.0 ± 249.6 vs. 347.2 ± 242.6 cGy, P-value = 0.010). Among right-sided patients or patients receiving anthracycline-based chemotherapy, the dual-targeted cohort had a higher risk of developing ECG abnormalities compared to the trastuzumab-only cohort., Conclusion: Compared with trastuzumab-only, dual anti-HER2 therapy does not increase early cardiac toxicity in combination with postoperative RT in BC patients. Cardiac radiation exposure remains the primary risk factor for early toxicity., Competing Interests: Conflicts of interest The authors have declared no conflicts of interest., (Copyright © 2025. Published by Elsevier Ltd.)

Background: Hepatitis B virus (HBV) surface antigen (HBsAg) seroprevalence was high before the national vaccine policy was introduced in Taiwan, indicating significant HBV infection rates. The success of the HBV immunization program and other preventive measures likely led to decreased HBsAg prevalence among pregnant women. This study reports on the HBV seroprevalence among pregnant women in Taiwan from 2016 to 2021, including those potentially affected by the universal hepatitis B vaccination at birth., Methods: This claim-based cohort study included pregnant women with hospital-based prenatal HBV screening data: 162,662 for HBsAg and 161,729 for HBeAg, from 2016 to 2021. Patient medical records were reviewed to collect information on demographic characteristics and other health conditions. Logistic regression models were used to identify risk factors associated with HBsAg and HBV e antigen (HBeAg) positivity., Results: The seroprevalence for HBsAg and HBeAg during the study period was 4.0% and 0.6%, respectively. HBsAg positivity was highest among women born before July 1984 (pre-vaccination period; 8.6%), decreasing to 2.2% among those born between July 1986 and 1988 (national vaccination implementation) and further declining to 1.1% for those born after 1997. These data underscore the crucial role of large-scale immunization strategies in controlling HBV infections. Similarly, HBeAg positivity was highest among pregnant women born before the vaccination program (~ 1.0%), decreasing significantly to 0.4% for those born after 1989. The results showed geographic variations, potentially reflecting factors such as the mother's age and foreign nationality. However, the birth year was the most crucial factor associated with HBV marker positivity., Conclusions: The implementation of national vaccination programs has demonstrated significant success in reducing HBV seroprevalence among pregnant women, which is particularly evident in the substantial decrease in HBsAg seroprevalence in Taiwan post-July 1986. These findings emphasize the importance of continued and consistent vaccination efforts, supporting the need for ongoing public health strategies to combat HBV infections effectively., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved on 20 April 2022 by the Taipei Medical University—Joint Institutional Review Board, with project number N202204052. Given the retrospective nature of the study using anonymized data from the National Health Insurance Research Database (NHIRD) in Taiwan, the requirement for informed consent was waived by the Taipei Medical University—Joint Institutional Review Board in accordance with local regulations and guidelines. Consent for publication: Not applicable. This manuscript does not contain any individual person’s data in any form, including individual details, images, or videos. Competing interests: Juan C. Vargas-Zambrano is an employee of Sanofi and declares no competing interests. Meng-Yun Ku and Li-Nien Chien have no competing interests to declare., (© 2025. The Author(s).)

Background: Longitudinal cognitive changes in Parkinson's disease (PD) exhibit considerable heterogeneity.Predicting cognitive trajectories in early PD patients can improve prognostic counseling and guide clinical trials., Methods: This study included 337 early PD patients with 6-year follow-up in the Parkinson's Progression Markers Initiative (PPMI) database.Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) to identify subtypes of longitudinal cognitive trajectories, and a nomogram predictive model was constructed using baseline clinical variables., Results: The 337 PD patients had a mean age of 61.0 years, mean disease duration of 0.55 years, and mean MoCA score of 27.1 points. Latent class mixed models (LCMM) identified two longitudinal cognitive subtypes: cognitive stable (276 cases, 81.9%) and cognitivel deteriorating (61 cases, 18.1%). The cognitively deteriorating subtype presented poorer baseline cognition, older age, and more severe motor and non-motor symptoms. On biomarkers, the cognitively deteriorating subtype revealed higher serum NFL levels and lower mean striatum DAT uptake. Six baseline clinical variables (age, Letter Number Sequencing score, Symbol Digit Modalities Test score, Benton Judgment of Line Orientation Test score, Hopkins Verbal Learning Test-Revised score, and REM Sleep Behavior Disorder) were selected to construct the nomogram predictive model which achieved an AUC of 0.92.The calibration curve demonstrated high consistency between predicted and observed probabilities.The predictive model has potential utility in disease-modifying clinical trials by pre-screening patients at high risk for cognitive deterioration., Conclusion: This study identified two longitudinal cognitive subtypes: cognitive stable and cognitive deterioration within 6-year follow-up, and eighteen percent of early PD patients shared the cognitive deterioration subtype The predictive model, incorporating six baseline variables could estimate the risk of longitudinal cognitive deterioration in PD., Competing Interests: Declarations. Ethical approval: The Ethics Standards Committee approved each participating in the PPMI for Human Experimentation before the start of the study. Informed consent: All subjects signed an informed consent form. Conflict of interest: The authors declare no competing interests., (© 2024. Fondazione Società Italiana di Neurologia.)

Ginsenoside compound K (GCK) has been proved to have great hypoglycemic effect pertinent to gut microbiota. However, the improvement of high-fat-diet (HFD)-induced type 2 diabetes (T2D) as well as the mechanism of GCK mediated by gut microbiota is not well-known. This study aimed to investigate the hypoglycemic effects and mechanism of GCK on a HFD-induced diabetic mouse model. HFD-induced pseudo-germ free (GF) T2D mice model and fecal microbiota transplantation (FMT) experiments were performed to clarify the role of gut microbiota in the hypoglycemic effect of GCK. Differential metabolites were screened by untargeted metabolomics analysis and their functions were verified by suppling to T2D mice. The level of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA analysis to explore the potential hypoglycemic mechanism of GCK. The results showed GCK alleviated metabolic disorders and altered gut microbiota in HFD-induced diabetic mice, which was transmitted to pseudo-GF diabetic mice via FMT experiment to reproduce the hypoglycemic effect. Non-targeted metabolites analysis on cecal content samples indicated that N-acetylserotonin (NAS) was markedly increased after GCK treatment. Moreover, gavage with NAS improved insulin sensitivity and increased the secretion of GLP-1 in HFD mice. Our study showed that GCK had hypoglycemic effect through modifying gut microbiota profiling., (© 2025 John Wiley & Sons Ltd.)

The globally vital oil palm, a major oil producer, confronts productivity challenges due to Ganoderma boninense (Gb), causing output decline. Chemical control efforts have proven ineffective, prompting exploration of microbial-based biocontrol. While single fungal biocontrol research exists, the impact of employing multiple biocontrols concurrently to combat Ganoderma and enhance oil palm growth remains uncharted. This study examined four soil-derived fungal isolates for their ability to antagonize Gb PER71 in vitro. Molecular identification categorized them as Talaromyces spp. and Penicillium sp. Moreover, all isolates were revealed to have at least three plant growth-promoting (PGP) traits and were shown to have phosphoric hydrolase, ester hydrolase, peptide hydrolase, and glycosidase activities which are essential for plant growth. Furthermore, the synergistic evaluation of fungal isolates was tested against Gb PER71. One out of six combinations of fungal isolates showed a synergistic effect in vitro, and two showed a synergistic effect in planta. The application of single and combined fungal isolates tested in planta also suppressed Gb PER71 and enhanced oil palm growth compared to control groups. The findings indicate the promising potential of these isolates as biocontrol agents (BCAs) and bioformulations against Gb in oil palm cultivation., (© 2024 Wiley‐VCH GmbH.)

Purpose: To investigate the clinical characteristics, treatment, and prognosis of patients with reflex epilepsies in Taiwan., Methods: Patients with reflex epilepsies (RE) induced by specific trigger factors from July 2000 to May 2024, were recruited at Chang Gung Memorial Hospital, Linkou, Taiwan. All patients had at least 12 months of follow-up. Demographic data, antiseizure medication (ASM) treatment, stimulus avoidance, and seizure outcome were analyzed. We further divided the patients into extrinsic and intrinsic RE groups based on the nature of stimuli. We also categorized them into ongoing seizure and seizure-free groups based on their seizure control. Fisher's exact test and Independent-Samples Mann-Whitney U Test were used to evaluate associations between clinical factors and prognosis. Multivariate logistic regression analysis was further carried out to determine the predictors of seizure outcomes., Results: In this study, 81 patients with reflex epilepsies (RE) were analyzed, focusing on those with extrinsic (photosensitive) and intrinsic (Mah-Jong-related) seizure triggers. Patients with extrinsic RE were significantly younger (mean age 40.4 years) than those with intrinsic RE (mean age 64.4 years, p < 0.001) and had a notably earlier onset of reflex seizures (21.9 years vs. 49.7 years, p < 0.001). A higher proportion of extrinsic RE patients experienced spontaneous seizures (98 %) compared to intrinsic RE (40 %). Abnormal EEG findings were more prevalent in the extrinsic group (94.1 %) than in the intrinsic group (66.7 %). Ninety-eight percent of patients with extrinsic RE were treated with antiseizure medications (ASMs), with an average of 2.2 ASMs per patient, compared to 73.3 % and 1.2 ASMs in patients with intrinsic RE. Furthermore, the rate of stimulus avoidance was significantly higher among those with intrinsic RE, at 43.3 % compared to 3.9 % in the extrinsic group (p < 0.001). Both groups achieved similar seizure-free outcomes (68.6 % in extrinsic vs. 63.3 % in intrinsic RE), but stimulus avoidance is independently associated with a reduced likelihood of ongoing seizures (p = 0.038), with an odds ratio (OR) of 0.110., Conclusion: Intrinsic RE exhibited a later onset of spontaneous and reflex seizures than extrinsic RE. Avoidance of seizure triggers was more frequent in intrinsic RE and among seizure-free patients, suggesting that stimulus avoidance is crucial for better seizure control and prognosis. On the other hand, patients with extrinsic RE had a lower rate of trigger avoidance but were more likely to receive ASM treatment, suggesting ASM is crucial for managing seizures due to challenges in avoiding environmental triggers. Despite these differences, both groups achieved similar seizure-free outcomes, underscoring the necessity for tailored management strategies based on the type of reflex seizures., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Evidence has revealed that oestrogen deprivation-induced osteolysis is microbiota-dependent and can be treated by probiotics. However, the underlying mechanism require further investigation. This study aims to provide additional evidence supporting the use of probiotics as an adjuvant treatment and to explore the pathophysiology of oestrogen-deprived osteolysis., Methods: Forty-five SD rats were randomly divided into five groups (n = 9). Rats from four groups were ovariectomised and treated with NS, calcium, probiotics, or calcium + probiotics, while one group underwent a sham operation and was treated with NS. The osteometabolic effects were evaluated, and the mechanistic role of the probiotic supplement was explored., Results: Intragastric administration of Bifidobacterium animalis subsp. lactis LPL-RH (LPL-RH) markedly suppressed osteoclastic activation and bone calcium loss by downregulating TRAP enzymatic activity, the OPG/RANKL ratio, and the downstream signalling pathway RANKL/TRAF6/NF-κB/NFATc1/TRAP in ovariectomised SD rats. LPL-RH also reduced CD4 + IL-17 A + T H 17 cells in the bone marrow, the pro-osteoclastogenic cytokine IL-17 A, pro-inflammatory molecules (LPS), and its binding protein (LBP) in the blood. LPL-RH restored intestinal ZO-1, occludin, claudin 2, claudin 12, and claudin 15, which improved ileal histopathology, reduced ileal oxidative stress, and attenuated the LPS-responsive TLR4/MyD88/NF-κB pathway. Furthermore, 16 S rRNA sequencing revealed that LPL-RH altered the faecal microbiome by reducing the relative abundance of S24-7 at the family level and promoting Prevotella and Bacteroides at the genus level., Conclusion: Collectively, LPL-RH suppressed osteoclastogenesis and osteolysis by modulating type 17 immunity and gut microbiome., Competing Interests: Declarations. Ethical approval: The animal experiments in this study were approved by ethical committee of Nanchang Royo Biotech Co., Ltd (Nanchang, P. R. China) (No. RYE2021110801). All animal experiments were conducted with minimal pain to follow Guide for the Care and Use of Laboratory Animals (NIH, USA). Consent for publication: All authors were consent for the publication of this article. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to examine the clinical features and assess the surgical outcomes of traumatic optic neuropathy in pediatric patients. A retrospective analysis was conducted on the clinical data of 15 cases (17 eyes) of traumatic optic neuropathy in pediatric patients aged 1 to 6 years between January 2015 and July 2024. Two of them presented with binocular trauma, resulting in a total of 17 affected eyes. The injuries were attributed to various causes: 4 cases resulted from falls, 5 from car accidents, and 6 from localized impact trauma. Of the 15 patients (17 eyes), 10 patients (12 eyes) demonstrated postoperative improvement. Preoperatively, 3 eyes had residual vision, all of which revealed improvement following surgery. Among the 14 eyes with no light perception, 9 exhibited postoperative improvement. In one case (1 eye), where the interval between trauma and surgery was within 7 days, treatment was effective postoperatively. In 14 cases (16 eyes), where the interval exceeded 7 days, 11 eyes revealed postoperative improvement. Radiologic examination revealed optic canal fractures or optic nerve swelling in 6 cases. All patients underwent surgical intervention: 1 patient (1 eye) underwent transnasal endoscopic left orbital apex decompression combined with left periorbital hematoma evacuation, while 14 patients (16 eyes) underwent transnasal endoscopic optic nerve decompression. Imaging assessments should be integrated into the diagnostic process to help in selecting the most appropriate surgical approach for pediatric patients with traumatic optic neuropathy. Transnasal endoscopic optic nerve decompression significantly enhances the prognosis in these cases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Recent studies have revealed that intratumoral microbiota is implicated in pancreatic cancer (PC), yet the spectra of intratumoral microbiota and their relationship with PC in Chinese patients remained to be clarified. In this study, tumor and paired paracancerous tissue from 53 patients were profiled by bacterial 16S rRNA gene sequencing. Both α- and β -diversity displayed significant differences between tumors and adjacent tissues, with higher diversity in tumors. Three bacteria phyla (Proteobacteria, Firmicutes, and Actinobacteria) were prevalent in both cancers and adjacent normal tissues. A high prevalence of Pseudomonas has been identified in the PC tumor microenvironment and was associated with prolonged overall survival. Furthermore, the results of in vitro experiments suggested that Pseudomonas fluorescens ( P. fluorescens ) could inhibit the proliferation and induce apoptosis of pancreatic cancer cells. These findings revealed distinctive microbial features of the PC tumors and normal tissues in Chinese populations and exhibited the antitumor potential of P. fluorescens in PC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Chitosan, as a kind of naturally occurring green and degradable material for the preservation of perishable foods, was investigated in this study with the objective of enhancing its preservation performances. Herein, lignin was modified using the solvent fractionation method (modified lignin, ML, including ML1-ML3), while natural clinoptilolite zeolite was modified using the alkali modification method (modified clinoptilolite zeolite, MCZ, including MCZ1-MCZ5). After optimizing the conditions, it was discovered that incorporating both ML3 and MCZ3 into pure chitosan-based membranes might be conducive to fabricate chitosan-based composite membranes for the preservation of perishable foods. As-prepared composite membranes possessed better visible light transmittance, antioxidant activity, and carbon dioxide/oxygen selectivity, resulting in improved preservation effects on the model perishable foods such as bananas, cherry tomatoes, and cheeses. These findings might indicate promising applications for chitosan-based composite membranes with modified lignin and zeolite in the field of eco-friendly degradable materials for the preservation of perishable foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Our purpose was to investigate and test the causal relationship between type 1 diabetes (T1D) and inflammatory bowel disease (IBD) and its major phenotypes, including ulcerative colitis (UC) and Crohn's disease (CD), in two large datasets., Methods: We obtained IBD samples from the largest publicly available genome-wide association study (GWAS), as well as the FinnGen database and the publicly accessible IEU GWAS database of T1D. We employed a two-sample Mendelian randomization approach to assess bidirectional causality using the inverse variance weighting (IVW) method as the primary outcome., Results: Genetic predisposition to T1D was associated with reduced risk of IBD (IVW: odds ratio (OR), 0.867; 95% confidence interval (CI), [0.852, 0.883]; P < 0.001), UC (OR = 0.879 [0.823, 0.939], P < 0.001), and CD (OR = 0.925 [0.872, 0.981], P = 0.009). The republication results found IBD genetically possessed negative association with T1D (OR = 0.781 [0.684, 0.891], P < 0.001). Additionally, a meta-analysis of results was conducted to prove the strong evidence between T1D and CD (OR = 0.95 [0.91, 0.98]; p = 0.01)., Conclusions: This study first demonstrated a causal effect of TID on the reduced risk of CD in the mendelian randomization study., Competing Interests: Compliance with ethical standards Ethics approval and Consent to participate No ethical approval from an ethics committee or Equator Network checklist was necessary as our study did not involve any human or animal research or observational studies. Our investigation utilized Mendelian randomization analysis and draw data from open databases. All of the projects and datasets cited in our study were approved by the respective ethics committees of the corresponding published articles. Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Different aminated starch (AS) [EEAS (introducing ethylenediamine into starch using cross-linking-etherification-amination method (CEA)), EPAS (introducing o-phenylenediamine using CEA), OEAS (introducing ethylenediamine using cross-linking-oxidation-amination method (COA)), and OPAS (introducing o-phenylenediamine using COA)] were synthesized. The AS-phenolic acids [gallic acid (GA), syringic acid (SA), and vanillic acid (VA)] conjugates were prepared by laccase-catalyzed reaction. The grafting efficiency of EEAS on GA, SA, and VA was 36.59%, 69.71%, and 68.85%, respectively. SA reduced the maximum depolymerization rate of EEAS. The relative crystallinity of EEAS and EPAS grafted phenolic acid increased, and their particles showed severe breakage in appearance. OEAS-phenolic acid conjugates lost its granular structure and behaved as flakes and lumps, while the surface of OPAS-phenolic acid conjugates remained smooth after grafting phenolic acid. GA increased the DPPH· scavenging efficiency of EEAS from 16.12% to 79.92%. The increased antioxidant capacity of the conjugates suggested that AS-phenolic acids conjugates have high potential for applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the relationship between physician-hospital integration within accountable care organizations (ACOs) and inpatient care utilization and expenditure., Data Sources: The primary data were Massachusetts All-Payer Claims Database (2009-2013)., Study Setting: Fifteen provider organizations that entered a commercial ACO contract with a major private payer in Massachusetts between 2009 and 2013., Study Design: Using an instrumental variable approach, the study compared inpatient care delivery between patients of ACOs demonstrating high versus low integration. We measured physician-hospital integration within ACOs by the proportion of primary care physicians in an ACO who billed for outpatient services with a place-of-service code indicating employment or practice ownership by a hospital. The study sample comprised non-elderly adults who had continuous insurance coverage and were attributed to one of the 15 ACOs. Outcomes of interest included total medical expenditure during an episode of inpatient care, length of stay (LOS) of the index hospitalization, and 30-day readmission. An inpatient episode was defined as 30, 45, and 60 days from the admission date., Data Collection/extraction Methods: Not applicable., Principal Findings: The study examined 33,535 admissions from patients served by the 15 ACOs. Average medical expenditure within 30 days of admission was $24,601, within 45 days was $26,447, and within 60 days was $28,043. Average LOS was 3.5 days, and 5.4% of patients were readmitted within 30 days. Physician-hospital integration was associated with a 10.6% reduction in 30-day expenditure (95% CI, -15.1% to -5.9%). Corresponding estimates for 45 and 60 days were - 9.7% (95%CI, -14.2% to -4.9%) and - 9.6% (95%CI, -14.3% to -4.7%). Integration was associated with a 15.7% decrease in LOS (95%CI, -22.6% to -8.2%) but unrelated to 30-day readmission rate., Conclusions: Our instrumental variable analysis shows physician-hospital integration with ACOs was associated with reduced inpatient spending and LOS, with no evidence of elevated readmission rates., (© 2024 Health Research and Educational Trust.)

Background: Walking and balance impairments, represented by freezing of gait and falls, are significant contributors to disability in advanced Parkinson's disease (PD) patients. However, the composite measure of the Walking and Balance Milestone (WBMS) has not been thoroughly investigated., Methods: This study included 606 early-stage PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, with a disease duration of less than 2 years and no WBMS at baseline. Patients were divided into a model development cohort (70 %) and a validation cohort (30 %) according to the enrollment site. Longitudinal follow-up data over a period of 12 years were analyzed., Results: Among all 606 patients, the estimated probability of being WBMS-free at the 5th and 10th year was 88 % and 60 %, respectively. Five clinical variables (Age, Symbol Digit Modalities Test (SDMT), postural instability and gait difficulty (PIGD) score, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS-I) score, and REM Sleep Behavior Disorder (RBD) were used to construct the Cox predictive model. The C-index of the model was 0.75 in the development cohort and 0.76 in the validation cohort. By optimizing the PIGD and MDS-UPDRS-I variables, an easy-to-use model was achieved with comparable predictive performance., Conclusion: A predictive model based on five baseline clinical measures (Age, SDMT, PIGD score, MDS-UPDRS-I score, RBD) could effectively estimate the risk of the WBMS in early PD patients. This model is valuable for prognostic counseling and clinical intervention trials for gait and balance impairment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

In sexual reproduction, selfish genetic elements known as killer meiotic drivers (KMDs) bias inheritance by eliminating gametes that do not carry them. The selective killing behavior of most KMDs can be explained by a toxin-antidote model, where a toxin harms all gametes while an antidote provides resistance to the toxin in carriers. This study investigates whether and how the KMD element tdk1 in the fission yeast Schizosaccharomyces pombe deploys this strategy. Intriguingly, tdk1 relies on a single protein product, Tdk1, for both killing and resistance. We show that Tdk1 exists in a nontoxic tetrameric form during vegetative growth and meiosis but transforms into a distinct toxic form in spores. This toxic form acquires the ability to interact with the histone reader Bdf1 and assembles into supramolecular foci that disrupt mitosis in noncarriers after spore germination. In contrast, Tdk1 synthesized during germination of carrier spores is nontoxic and acts as an antidote, dismantling the preformed toxic Tdk1 assemblies. Replacement of the N-terminal region of Tdk1 with a tetramer-forming peptide reveals its dual roles in imposing an autoinhibited tetrameric conformation and facilitating the assembly of supramolecular foci when autoinhibition is released. Moreover, we successfully reconstituted a functional KMD element by combining a construct that exclusively expresses Tdk1 during meiosis ("toxin-only") with another construct that expresses Tdk1 specifically during germination ("antidote-only"). This work uncovers a remarkable example of a single protein employing structural duality to form a toxin-antidote pair, expanding our understanding of the mechanisms underlying toxin-antidote systems., Competing Interests: Competing interests statement:The authors declare no competing interest.

Killer meiotic drivers (KMDs) are selfish genetic elements that distort Mendelian inheritance by selectively killing meiotic products lacking the KMD element, thereby promoting their own propagation. Although KMDs have been found in diverse eukaryotes, only a limited number of them have been characterized at the molecular level, and their killing mechanisms remain largely unknown. In this study, we identify that a gene previously deemed essential for cell survival in the fission yeast Schizosaccharomyces pombe is a single-gene KMD. This gene, tdk1 , kills nearly all tdk1Δ progeny in a tdk1+ × tdk1Δ cross. By analyzing polymorphisms of tdk1 among natural strains, we identify a resistant haplotype, HT3. This haplotype lacks killing ability yet confers resistance to killing by the wild-type tdk1 . Proximity labeling experiments reveal an interaction between Tdk1, the protein product of tdk1 , and the epigenetic reader Bdf1. Interestingly, the nonkilling Tdk1-HT3 variant does not interact with Bdf1. Cryoelectron microscopy further elucidated the binding interface between Tdk1 and Bdf1, pinpointing mutations within Tdk1-HT3 that disrupt this interface. During sexual reproduction, Tdk1 forms stable Bdf1-binding nuclear foci in all spores after meiosis. These foci persist in germinated tdk1Δ progeny and impede chromosome segregation during mitosis by generating aberrant chromosomal adhesions. This study identifies a KMD that masquerades as an essential gene and reveals the molecular mechanism by which this KMD hijacks cellular machinery to execute killing. Additionally, we unveil that losing the hijacking ability is an evolutionary path for this single-gene KMD to evolve into a nonkilling resistant haplotype., Competing Interests: Competing interests statement:The authors declare no competing interest.

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE -/- ) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg -1 ·d -1 , i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 μM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE -/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The carbon-neutral target presents a significant challenge for the sewage sludge treatment and disposal (SSTD) industry, necessitating strategic planning for a low-carbon transition. However, flexible and comprehensive carbon emission analysis tools to support this goal remain lacking. This study presents a carbon emission analysis tool to evaluate the carbon emission characteristics and future mitigation potentials of SSTD. The tool integrates life cycle inventory (LCI) modeling-based analysis, sensitivity analysis, regression analysis, and scenario analysis. Carbon emissions are dynamically calculated based on sludge properties, technological level, and industry external parameters, providing a foundation for adaptable evaluation tailored to local conditions. The framework considers the potential effects of multi-parameter and multi-aspect changes in scene design, both within and outside the industry, to achieve dynamic and comprehensive simulations. A case study conducted in Wuhan, China, demonstrated the usability and application processes of the framework. The results indicated that carbon emissions from SSTD are projected to more than double from 2021 to 2060 without interventions. Among the mitigation measures, energy and chemical savings would yield the largest reduction potential, followed by the technical layout adjustment and the promotion of energy efficiency. Operational optimization in the sludge industry and outside the industry would contribute the least. With all mitigation measures applied, emissions could decrease to -82.91 kt CO 2-eq in 2060, equivalent to 13.03% compensation for emissions from the sewage treatment line. Among all the processes, incineration routes are recommended due to their current and future low carbon emissions. The cooperative resource route of anaerobic digestion and land use also shows promise as it progressively demonstrates superior performance with increasing organic matter and nutrient content of sludge. Critical factors, sub-processes, and emission types for different routes were identified and can be optimized accordingly. The developed method demonstrates sufficient flexibility to be applied to other cities and larger-scale regions, thereby offering technical and strategic support for SSTD towards carbon-neutral operation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to investigate the effect of remote ischemic preconditioning (RIPC) on the healing of small intestinal anastomoses, evaluated by tensile strength and histologic wound healing on postoperative day 5., Methods: A total of 22 female pigs were randomized 1:1 into either an intervention or control group. The intervention group received 5 cycles of 3-minute ischemia followed by 3-minute reperfusion on the right forelimb. Two end-to-end anastomoses, a distal and a proximal, were created in the small intestine 30 and 60 min after RIPC, respectively. On postoperative day 5, the anastomoses were harvested and underwent a maximal anastomotic tensile strength (MATS) test (MATS 1-3) followed by histologic analyses., Results: MATS 1, when a tear became visible in the serosa, was significantly increased in the proximal anastomoses of the RIPC group compared with the control group (4.91 N vs 3.83 N; P = .005). No other significant differences were found when comparing these 2 groups., Conclusion: Our study showed no convincing results of RIPC on intestinal anastomotic healing to recommend its use in a general clinical setting. Further animal studies on RIPC's effect after relative or absolute intestinal ischemia may be recommended., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bile acids (BAs) exert a profound influence on the body's pathophysiology by intricately shaping the composition of gut bacteria. However, the complex interplay between BAs and gut microbiota has impeded a systematic exploration of their impact on intestinal bacteria. Initially, we investigated the effects of 21 BAs on the growth of 65 gut bacterial strains in vitro. Subsequently, we examined the impact of BAs on the overall composition of intestinal bacteria, both in vivo and in vitro. The results unveiled distinct effects of various BAs on different intestinal strains and their diverse impacts on the composition of gut bacteria. Mechanistically, the inhibition of intestinal strains by BAs occurs through the accumulation of these acids within the strains. The intracellular accumulation of deoxycholic acid (DCA) significantly influenced the growth of intestinal bacteria by impacting ribosome transcription and amino-acid metabolism. The metabolomic analysis underscores the pronounced impact of DCA on amino-acid profiles in both in vivo and in vitro settings. This study not only elucidates the effects of BAs on a diverse range of bacterial strains and their role in shaping the gut microbiota but also reveals underlying mechanisms essential for understanding and maintaining a healthy gut microbiota., (© 2024. The Author(s).)

This study evaluates the survival outcomes of segmental ureterectomy (SU) combined with chemotherapy in patients with high-grade non-metastatic ureteral cancer (UC) using data from the SEER database. A total of 1757 patients with Grade III-IV non-metastatic UC were analyzed. Overall survival (OS) was assessed through Kaplan-Meier analysis, and independent prognostic factors were identified via Cox regression. A Nomogram model was developed and evaluated using the concordance index, area under the time-dependent ROC curve, calibration curves, and decision curve analysis. The 1-, 3-, and 5-year OS rates were 82.8%, 55.6%, and 42.8%, respectively. Age, treatment protocol, T stage, and N stage were significant prognostic factors. Both SU + chemotherapy and radical nephroureterectomy (RNU) + chemotherapy demonstrated comparable survival outcomes, outperforming surgery alone, particularly in patients aged 70 and older. The Nomogram demonstrated high predictive accuracy and clinical utility. These findings suggest that SU + chemotherapy offers survival benefits similar to RNU + chemotherapy, making it a viable option, especially for elderly patients or those with impaired renal function., (© 2024. The Author(s).)

Introduction: Medical postgraduates generally experience high levels of depression and anxiety. Previous studies have investigated the impact of various achievement motivations on depression/anxiety among medical students., Methods: This study focused on self-esteem and perceived stress, examining the internal mechanisms through which achievement motivation affects depression/anxiety. 530 medical postgraduate students (66.04% female and 33.96% male) were administered the Achievement Goal Orientation Scale, Self-Esteem Scale, Perceived Stress Scale, and Depression-Anxiety-Stress Scale., Results: Results indicated that: (1) mastery-approach goals were negatively correlated with depression/anxiety; mastery-avoidance goals were positively correlated with depression/anxiety; performance-avoidance goals positively predicted depression/anxiety; (2) self-esteem mediated the relationship between achievement motivation and depression/anxiety; (3) perceived stress played a mediating role in the relationship between achievement motivation and depression/anxiety; (4) self-esteem and perceived stress played a chain mediating role in the relationship between achievement motivation and depression/anxiety; (5) there was no significant linear correlation between mastery-approach goals and depression/anxiety., Discussion: Although this study employed a cross-sectional design and self-report scales, both of which have certain limitations, the findings still hold significant theoretical and practical implications. The research reveals a mediating pathway between achievement goals and mental health, offering new insights into mental health education for medical graduate students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Li, Guo and Yang.)

Importance: Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential., Objective: To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC., Design, Setting, and Participants: This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9)., Main Outcomes and Measures: The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping., Results: Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects., Conclusion and Relevance: The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Background: This study aims to explore the protective role of JB-V-60-a novel synthetic derivative of decur-sin-against lipopolysaccharide (LPS)-induced inflammation., Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice., Results: JB-V-60 enhanced HO-1 levels, inhibited NF-κB activation, reduced COX-2/PGE2 and iNOS/NO concentra-tions, and lowered phosphorylation of signal transducer and activator of transcription 1. It also promoted the translocation of Nrf2 into the nucleus, allowing its binding to antioxidant response elements and resulting in reduced IL-1β in LPS-stimulated HPAECs. The reduction in iNOS/NO levels by JB-V-60 was reversed when HO-1 was inhibited via RNAi. In the animal model, JB-V-60 sig-nificantly decreased iNOS expression in lung tissues and TNF-α levels in bronchoalveolar lavage fluid., Conclusions: These findings highlight the anti-inflammatory effects of JB-V-60 and its potential as a treat-ment for inflammatory disorders.

Background: Cardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF., Methods: We conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction < 50 %, without HF symptoms, signs, or prior HF hospitalization. CPO was derived from invasive hemodynamic parameters. Endpoints included HF hospitalization, cardiovascular mortality, and all-cause mortality over a 5-year follow-up., Results: A total of 783 coronary artery disease patients with ALVSD at stage B HF were enrolled. Incidence rates (per 1000 person-years) were 13.9 for HF hospitalization, 14.5 for cardiovascular mortality, and 23.7 for all-cause mortality.Multivariate analysis adjusting for covariates demonstrated that CPO was independent associated with all endpoints. Patients with a low CPO (<0.97 Watts) were at significantly higher risk for HF hospitalization (adjusted hazard ratio [HR]: 4.04; 95 % CI: 1.53 - 10.6; p = 0.005), cardiovascular mortality (adjusted HR: 2.73; 95 % CI: 1.19 - 6.27; p = 0.018), and all-cause mortality (adjusted HR: 1.86; 95 % CI: 1.05 - 3.30; p = 0.035) compared to those with higher CPO, regardless of subgroup classification., Conclusion: Resting CPO in patients with ALVSD is significantly associated with adverse events, including HF hospitalization and mortality, highlighting its value in early-stage HF management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Dental pulp inflammation is a common and significant factor related to poor dental prognosis. Current treatment strategies primarily concentrate on managing the inflammatory response, with specific targets for intervention still under investigation. Triggering receptors expressed on myeloid cells (TREMs) are a group of receptor molecules extensively present on myeloid cell surfaces, crucial in the regulation of inflammatory process. Our analysis of transcriptomic sequencing data from clinical pulp samples of dataset GSE77459 and animal models revealed up-regulation of Trem1 during pulpitis. Administration of the Trem1-blocking peptide LP17 led to lower (more than 1-fold) levels of several pro-inflammatory factors and inhibition of M1 macrophage polarization both in vivo and in vitro. This study of the expression patterns and functions of Trem1 in the development of dental pulp inflammation provides novel insights into the therapeutic strategies for clinical pulpitis., (© 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Objective: Among motor vehicle crashes (MVCs), little is known about whether the characteristics and collision features involving drivers with epilepsy differ from those involving drivers without any history of epilepsy. We assessed MVC features and the effect of epilepsy diagnosis on the risk of severe crash-related injuries among drivers., Methods: A total of 33 174 MVC events among people with epilepsy (PWE) and 663 480 MVC events of age- and sex-matched non-PWE (1:20) were selected. Crash-related features that involved drivers with and without epilepsy were compared, including driver eligibility, medical history of comorbidities and medications, road and environmental conditions, and accident causes. Cox and logistic regression analyses were used to examine the risks of fatality and severe injury among drivers with and without epilepsy., Results: PWE involved in MVCs were more likely to have lower socioeconomic status, comorbidities, scooter drivers without a qualified driver's license, driving under the influence of alcohol, and be involved in single-vehicle accidents than non-PWE. Drivers with epilepsy also had a higher risk of fatality within 30 days of MVC, with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI], 1.20-1.57) and a higher risk of hospital admission within 3 days after MVC (aHR, 1.33; 95% CI, 1.29-1.38) compared to that of non-PWE., Significance: The characteristics of MVCs of drivers with epilepsy were distinct from those of non-affected drivers. And higher fatality and injury rates were observed among drivers with epilepsy, which should be considered in further policymaking regarding safe driving of PWE., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed., Methods: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database., Results: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility., Conclusion: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The clinical value of therapeutic drug monitoring (TDM) for newer anti-seizure medications (ASMs) remains uncertain. This study aimed to assess the impact of newer ASM TDM on clinical decision making in patients with epilepsy., Methods: We retrospectively identified all plasma requests for newer ASM level measurement as part of routine clinical management in the outpatient departments of seven medical institutes across Taiwan between September 2016 and May 2019. Data collected from reviewed medical records included clinical and medication details, indications for TDM requests, test results, interpretation, and impact on patient management., Results: A total of 682 visits with 1051 plasma samples were included. The most frequently analyzed ASMs were levetiracetam (36.1%), oxcarbazepine (18.4%), and lamotrigine (12.0%). Reasons for TDM included poorly controlled seizures (55.3%), concerns about drug-drug interactions (12.3%), and suspicion of drug overdose (10.6%). 68.8% of samples were within the orienting therapeutic range, even for patients with poorly controlled seizures. TDM for non-adherence concerns showed 54.3% below the orienting therapeutic range, while ASM-related adverse events assessment only 8.9% showed levels exceeding the orienting therapeutic range. Following TDM results, 64.2% of cases had medication adjustments, mainly dosage increases. Overall, 55.9% of newer ASM TDM visits showed improved outcomes, including reduced seizures (47.5%) and fewer ASM-related side effects (8.4%)., Conclusions: These findings suggest that appropriate utilization of TDM for newer ASMs provides clinical benefits in adjunct to complement clinical decision making in the management of epilepsy patients in a real-world clinical setting., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objective: Hemodynamic monitoring via right heart catheterization (RHC) is critical for managing acute coronary syndrome (ACS) patients with heart failure or cardiogenic shock. However, the prognostic value of RHC-derived hemodynamic indices in ACS patients with left ventricular systolic dysfunction (LVSD) but without heart failure or shock remains uncertain., Methods: A retrospective cohort study included 1151 consecutive ACS patients who underwent RHC during hospitalization from 2007 to 2016. After excluding patients with shock, pulmonary edema, and severe valvular disease, 750 ACS patients with LVSD and ejection fraction < 50% were analyzed. Major adverse cardiovascular events (MACEs), including myocardial infarction and all-cause mortality, were followed for five years. Cox regression identified predictors of MACEs, adjusting for comorbidities, treatments, and hemodynamic indices, including pulmonary arterial capacitance (PAC)., Results: After a mean follow-up of 4.0 ± 1.7 years, 113 (15.1%) patients experienced MACEs. Multivariate analysis showed that independent predictors included prior stroke, calcified coronary lesions, and PAC. Patients in the lowest PAC tertile (≤2.89 ml/mmHg) had significantly higher risks of myocardial infarction (adjusted hazard ratio [HR]: 3.74; 95% confidence interval [CI]: 1.55-9.07; p  = .003), all-cause mortality (adjusted HR: 2.55; 95% CI: 1.27-5.10; p  = .008), and MACEs (adjusted HR: 2.35; 95% CI: 1.25-4.42; p  = .008) compared to those in the highest tertile (>4.43 ml/mmHg)., Discussion: The study demonstrated that PAC is a notably strong hemodynamic parameter with independent long-term prognostic value in ACS patients with LVSD, who do not present with shock or heart failure. This is the first study to establish the prognostic significance of hemodynamic indices obtained from RHC in this population, extending the clinical relevance of RHC from high-risk to intermediate-risk ACS populations., Conclusions: The use of RHC to assess hemodynamic indices, including PAC, during index hospitalization in this population may enhance long-term risk stratification and improve outcome prediction., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background : Pompe disease is a rare metabolic myopathy caused by the lack or deficiency of the lysosomal acid alpha-glucosidase, resulting in skeletal muscle weakness and cardiomyopathy. The disease varies by onset age and genetic mutations and is categorized into infantile-onset and late-onset Pompe disease. Respiratory muscle weakness may persist regardless enzyme replacement therapy. This systemic review and meta-analysis aim to assess the effect of respiratory muscle training (RMT) on respiratory muscle strength, functional endurance, and pulmonary function in patient with Pompe disease. Methods : PubMed, EMBASE, and Cochrane databases were searched up until Aug 2024. Studies examining the therapeutic effects of RMT in patients with Pompe disease were included. Outcome measures included the change in maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), six-minute walking test (6MWT), pulmonary function before after RMT, quality of life and adverse events. Results : The meta-analysis consisted of 5 single-arm studies, including 31 patients in total. Regarding inspiratory muscle strength, RMT has significantly improving MIP (8.71 cmH 2 O; 95% CI, 6.23-11.19, p < 0.001) and MEP (12.15 cmH 2 O; 95% CI, 10.55-13.74, p < 0.001) in both types of Pompe disease. However, no significant change regarding 6MWT. No serious adverse events were reported. Conclusions : Our meta-analysis revealed that RMT may increase inspiratory muscle and expiratory muscle strength, but may not have an effect on 6MWT in patients with Pompe disease. RMT has potential to be integrated into the cardioplulmonary rehabilitation for patients with Pompe disease. Further large randomized controlled trials are needed to verify the efficacy and safety of RMT in patients with Pompe disease., Competing Interests: The authors declare no conflicts of interest.

Electronic cigarettes (e-cigarettes) have been advertised as a healthier alternative to traditional cigarettes; however, their exact effects on the bronchial epithelium are poorly understood. Air-liquid interface culture human bronchial epithelium (ALI-HBE) contains various cell types, including basal cell, ciliated cell and secretory cell, providing an in vitro model that simulates the biological characteristics of normal bronchial epithelium. Multiplex single-cell RNA sequencing of ALI-HBE was used to reveal previously unrecognized transcriptional heterogeneity within the human bronchial epithelium and cell type-specific responses to acute exposure to e-cigarette aerosol (e-aerosol) containing distinct components (nicotine and/or flavoring). The findings of our study show that nicotine-containing e-aerosol affected gene expression related to transformed basal cells into secretory cells after acute exposure; inhibition of secretory cell function by down-regulating genes related to epithelial cell differentiation, calcium ion binding, extracellular exosomes, and secreted proteins; and enhanced interaction between secretory cells and other cells. On the other hand, flavoring may alter the growth pattern of epithelial cells and make basal cells more susceptible to SARS-CoV infection. Besides, the data also indicate factors that may promote SARS-CoV-2 infection and suggest therapeutic targets for restoring normal bronchial epithelium function after e-cigarette use. In summary, the current study offered fresh perspectives on alterations in the cellular landscape and cell type-specific responses in human bronchial epithelium that are brought about by e-cigarette use., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wing-Hung Ko reports financial support was provided by Research Grant Council General Research Fund. Wing-Hung Ko reports financial support was provided by Health and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region. Xiaofan Mao reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Nasolabial fold formation is increasingly becoming a cause of concern for many people. However, no network meta-analysis has compared the efficacy of different fillers in treating nasolabial folds. This network meta-analysis simultaneously compared the efficacy and safety of various fillers., Methods: We included randomized controlled trials (RCTs) that used fillers to treat nasolabial folds. We extracted data of Wrinkle Severity Rating Scale (WSRS), Global Esthetic Improvement Scale (GAIS, investigator) scores, GAIS scores (self-reported) and adverse events., Results: We included 13 RCTs. WSRS scores at 6 months were higher in patients receiving HA than those receiving poly (L-lactic acid) (mean difference [MD] 0.630, 95% confidence interval [CI] 0.275, 0.985) but significantly lower in patients receiving HA than in those receiving bovine collagen (MD - 0.580, 95% CI - 0.777, - 0.383) and porcine collagen (MD - 0.525, 95% CI - 0.790, - 0.260). Regarding adverse events, HA was significantly less likely to cause nodule formation compared with bovine collagen (RR 0.593, 95% CI 0.438, 0.803)., Conclusion: HA is a safe filler for correcting nasolabial folds, and poly (L-lactic acid) showed potential in treating nasolabial folds., Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background and Objectives: Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3-12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes., Methods: This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed., Results: The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016)., Conclusion: Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD., (© 2024. The Author(s).)

Objective: This study aimed to explore the influence of different spontaneous breathing trials (SBTs) on regional ventilation distribution in patients with prolonged mechanical ventilation (PMV)., Methods: A total of 24 patients with PMV were analyzed retrospectively. They received three different SBT modes which are automatic tube compensation (ATC), continuous positive airway pressure (CPAP), and T-piece (TP), over three days, and every SBT lasted two hours. Electrical impedance tomography (EIT) was used to monitor the SBT process and five-minute EIT data from five periods (pre-SBT which is t0, at the beginning and the end of the first hour SBT are t1 and t2, at the beginning and the end of the second hour SBT are t3 and t4) were analyzed., Results: In all PMV patients, the temporal skew of aeration (TSA) values at t3 were significantly different in three SBTs (ATC: 18.18±22.97; CPAP: 20.42±17.01; TP:11.26±11.79; p=0.05). In the weaning success group, TSA (t1) values were significantly different too (ATC: 11.11±13.88; CPAP: 19.09±15.77; TP: 9.09±12.74; p=0.04). In the weaning failure group, TSA (t4) values were significantly different in three SBTs (ATC: 36.67±18.46; CPAP: 15.38±11.69; TP: 17.65±17.93; p=0.04). The patient's inspiratory effort (Global flow index at t1) in patients with weaning failure under CPAP (3.51±4.31) was significantly higher than that in the ATC (1.15±1.47) and TP (0.89±1.28). The SBT mode with the best ventilation uniformity may be the one that activates the respiratory muscles the most which may be the optimal SBT. The SBT mode of most uniform ventilation distribution settings varies from patient to patient., Conclusion: The regional ventilation distribution was different for each individual, making the SBT with the best ventilation distribution of patients need to be personalized. EIT is a tool that can be considered for real-time assessment., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Herein, we evaluated the optimal timing for implementing the BioFire ® FilmArray ® Pneumonia Panel (FA-PP) in the medical intensive care unit (MICU). Respiratory samples from 135 MICU-admitted patients with acute respiratory failure and severe pneumonia were examined using FA-PP. The cohort had an average age of 67.1 years, and 69.6% were male. Notably, 38.5% were smokers, and the mean acute physiology and chronic health evaluation-II (APACHE-II) score at initial MICU admission was 30.62, and the mean sequential organ failure assessment score (SOFA) was 11.23, indicating sever illness. Furthermore, 28.9, 52.6, and 43% of patients had a history of malignancy, hypertension, and diabetes mellitus, respectively. Community-acquired pneumonia accounted for 42.2% of cases, whereas hospital-acquired pneumonia accounted for 37%. The average time interval between pneumonia diagnosis and FA-PP implementation was 1.9 days, and the mean MICU length of stay was 19.42 days. The mortality rate was 50.4%. Multivariate logistic regression analysis identified two variables as significant independent predictors of mortality: APACHE-II score ( p = 0.033, OR = 1.06, 95% CI 1.00-1.11), history of malignancy (OR = 3.89, 95% CI 1.64-9.26). The Kaplan-Meier survival analysis indicated that early FA-PP testing did not provide a survival benefit. The study suggested that the FA-PP test did not significantly impact the mortality rate of patients with severe pneumonia with acute respiratory failure. However, a history of cancer and a higher APACHE-II score remain important independent risk factors for mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Chou, Wang, Yang, Lai, Chang and Chang.)

Background: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs., Study Designs and Methods: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood-transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow-up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between-cohort risk differences, a Kaplan-Meier survival analysis and multiple Cox proportional hazard model was used., Results: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non-TR group. The risk of VTE or PE was twice as high in the TR group than in the non-TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49-4.29, p = .001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism., Conclusion: TRs are associated with increased long-term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow-up., (© 2024 AABB.)

Objectives: Manual compression (MC) or vascular closure devices (VCDs) are used to achieve hemostasis after percutaneous transluminal angioplasty (PTA). However, limited data on the comparative safety and effectiveness of VCDs vs MC in patients with end-stage renal disease (ESRD) undergoing PTA are available. Accordingly, this study compared the safety and effectiveness of VCD and MC in patients with ESRD undergoing PTA., Methods: This single-center retrospective cohort study included the data of patients with ESRD undergoing peripheral intervention at Chang Gung Memorial Hospital, Taiwan, from January 1, 2019, to June 30, 2022. The patients were divided into VCD and MC groups. The primary endpoint was a composite of puncture site complications, including acute limb ischemia, marked hematoma, pseudoaneurysm, and puncture site bleeding requiring blood transfusion., Results: We included 264 patients with ESRD undergoing PTA, of whom 60 received a VCD and 204 received MC. The incidence of puncture site complications was 3.3% in the VCD group and 4.4% in the MC group (hazard ratio: .75; 95% confidence interval: .16-3.56 L P = 1.000), indicating no significant between-group difference., Conclusion: VCDs and MC had comparable safety and effectiveness for hemostasis in patients with ESRD undergoing peripheral intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex. We solve the structure of the seipin/Adig complex by Cryo-EM at 2.98Å overall resolution. Surprisingly, seipin can form two unique oligomers, undecamers and dodecamers. Adig selectively binds to the dodecameric seipin complex. We further find that Adig promotes seipin assembly by stabilizing and bridging adjacent seipin subunits. Functionally, Adig plays a key role in generating lipid droplets in adipocytes. In mice, inducible overexpression of Adig in adipocytes substantially increases fat mass, with enlarged lipid droplets. It also elevates thermogenesis during cold exposure. In contrast, inducible adipocyte-specific Adig knockout mice manifest aberrant lipid droplet formation in brown adipose tissues and impaired cold tolerance.